A series of compounds based on the natural alkaloid colchicine were examined in the NCI P388 lymphocytic leukemia screen in mice and for their affinity to tubulin. The toxicities of the compounds were examined and compared. In general, a direct relationship between tubulin binding and in vivo activity was not found, but the binding affinity of new colchicine-like molecules to tubulin could be utilized in the search for new anti-cancer drugs. The combined pharmacological information has indicated that molecules formed by a triplet of chemical changes in colchicine may result in potent compounds with lessened toxicity. Congeners of colchicine, containing an N-hydroxyacetyl group instead of the usual N-acetyl group, have been found among natural products. The synthesis of one of them, colchifoline, has been accomplished.